Glyphosate Separating and Sensing for Precision Agriculture and Environmental Protection in the Era of Smart Materials.

The present article critically and comprehensively reviews the most recent reports on smart sensors for determining glyphosate (GLP), an active agent of GLP-based herbicides (GBHs) traditionally used in agriculture over the past decades. Commercialized in 1974, GBHs have now reached 350 million hectares of crops in over 140 countries with an annual turnover of 11 billion USD worldwide. However, rolling exploitation of GLP and GBHs in the last decades has led to environmental pollution, animal intoxication, bacterial resistance, and sustained occupational exposure of the herbicide of farm and companies' workers. Intoxication with these herbicides dysregulates the microbiome-gut-brain axis, cholinergic neurotransmission, and endocrine system, causing paralytic ileus, hyperkalemia, oliguria, pulmonary edema, and cardiogenic shock. Precision agriculture, i.e., an (information technology)-enhanced approach to crop management, including a site-specific determination of agrochemicals, derives from the benefits of smart materials (SMs), data science, and nanosensors. Those typically feature fluorescent molecularly imprinted polymers or immunochemical aptamer artificial receptors integrated with electrochemical transducers. Fabricated as portable or wearable lab-on-chips, smartphones, and soft robotics and connected with SM-based devices that provide machine learning algorithms and online databases, they integrate, process, analyze, and interpret massive amounts of spatiotemporal data in a user-friendly and decision-making manner. Exploited for the ultrasensitive determination of toxins, including GLP, they will become practical tools in farmlands and point-of-care testing. Expectedly, smart sensors can be used for personalized diagnostics, real-time water, food, soil, and air quality monitoring, site-specific herbicide management, and crop control.

Protein Determination with Molecularly Imprinted Polymer Recognition Combined with Birefringence Liquid Crystal Detection.

Liquid crystal-based sensors offer the advantage of high sensitivity at a low cost. However, they often lack selectivity altogether or require costly and unstable biomaterials to impart this selectivity. To incur this selectivity, we herein integrated a molecularly imprinted polymer (MIP) film recognition unit with a liquid crystal (LC) in an optical cell transducer. We tested the resulting chemosensor for protein determination. We examined two different LCs, each with a different optical birefringence. That way, we revealed the influence of that parameter on the sensitivity of the (human serum albumin)-templated (MIP-HSA) LC chemosensor. The response of this chemosensor with the (MIP-HSA)-recognizing film was linear from 2.2 to 15.2 µM HSA, with a limit of detection of 2.2 µM. These values are sufficient to use the devised chemosensor for HSA determination in biological samples. Importantly, the imprinting factor (IF) of this chemosensor was appreciable, reaching IF = 3.7. This IF value indicated the predominant binding of the HSA through specific rather than nonspecific interactions with the MIP.

Selective PQQPFPQQ Gluten Epitope Chemical Sensor with a Molecularly Imprinted Polymer Recognition Unit and an Extended-Gate Field-Effect Transistor Transduction Unit.

A molecularly imprinted polymer (MIP) recognition system was devised for selective determination of an immunogenic gluten octamer epitope, PQQPFPQQ. For that, a thin MIP film was devised, guided by density functional theory calculations, and then synthesized to become the chemosensor recognition unit. Bis(bithiophene)-based cross-linking and functional monomers were used for this synthesis. An extended-gate field-effect transistor (EG-FET) was used as the transduction unit. The EG-FET gate surface was coated with the PQQPFPQQ-templated MIP film, by electropolymerization, to result in a complete chemosensor. X-ray photoelectron spectroscopy analysis confirmed the presence of the PQQPFPQQ epitope, and its removal from the MIP film. The chemosensor selectively discriminated between the octamer analyte and another peptide of the same number of amino acids but with two of them mismatched (PQQQFPPQ). The chemosensor was validated with respect to both the PQQPFPQQ analyte and a real gluten extract from semolina flour. It was capable to determine PQQPFPQQ in the concentration range of 0.5-45 ppm with the limit of detection (LOD) = 0.11 ppm. Moreover, it was capable of determining gluten in real samples in the concentration range of 4-25 ppm with LOD = 4 ppm, which is a value sufficient for discriminating between gluten-free and non-gluten-free food products. The gluten content in semolina flour determined with the chemosensor well correlated with that determined with a commercial ELISA gluten kit. The Langmuir, Freundlich, and Langmuir-Freundlich isotherms were fitted to the epitope sorption data. The sorption parameters determined from these isotherms indicated that the imprinted cavities were quite homogeneous and that the epitope analyte was chemisorbed in them.

Molecularly Imprinted Polymer Chemosensor for Selective Determination of an N-Nitroso-l-proline Food Toxin.

A molecularly imprinted polymer (MIP)-based chemosensor for the selective determination of a chosen toxin, N-nitroso-l-proline (Pro-NO), was devised and fabricated. By means of DFT, the structure of the pre-polymerization (functional monomer)-template complex was modeled. This complex was then potentiodynamically electropolymerized in the presence of cross-linking monomer to form a MIP-Pro-NO thin film. Next, the Pro-NO template was extracted from MIP-Pro-NO with 0.1 m NaOH. Piezoelectric microgravimetry (PM) on an electrochemical quartz crystal microbalance and electrochemical (differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy (EIS)) techniques were used to transduce binding of Pro-NO to molecular cavities of the MIP-Pro-NO. With DPV and EIS chemosensing, the limits of detection (LODs) were about 80.9 and 36.9 nM Pro-NO, respectively; and the selectivity coefficients for urea, glucose, creatinine, and adrenalin interferences were 6.6, 13.2, 2.1, and 2.0, respectively, with DPV as well as 2.3, 2.0, 3.3, and 2.5, respectively, with EIS. With PM under flow injection analysis conditions, the LOD was 10 µm Pro-NO. The MIP-Pro-NO chemosensor detectability and selectivity with respect to interferences were sufficiently high to determine Pro-NO in protein-providing food products.

Potential-driven chirality manifestations and impressive enantioselectivity by inherently chiral electroactive organic films.

The typical design of chiral electroactive materials involves attaching chiral pendants to an electroactive polyconjugated backbone and generally results in modest chirality manifestations. Discussed herein are electroactive chiral poly-heterocycles, where chirality is not external to the electroactive backbone but inherent to it, and results from a torsion generated by the periodic presence of atropisomeric, conjugatively active biheteroaromatic scaffolds, (3,3'-bithianaphthene). As the stereogenic element coincides with the electroactive one, films of impressive chiroptical activity and outstanding enantiodiscrimination properties are obtained. Moreover, chirality manifestations can be finely and reversibly tuned by the electric potential, as progressive injection of holes forces the two thianaphthene rings to co-planarize to favor delocalization. Such deformations, revealed by CD spectroelectrochemistry, are elastic and reversible, thus suggesting a breathing system.

Molecularly imprinted polymer for recognition of 5-fluorouracil by RNA-type nucleobase pairing.

A 6-aminopurine (adenine) derivative of bis(2,2'-bithienyl)methane, vis., 4-[2-(6-amino-9H-purin-9-yl)ethoxy]phenyl-4-[bis(2,2'-bithienyl)methane] or Ade-BTM, was designed and synthesized for recognition of 5-fluorouracil (FU), an antitumor chemotherapy agent, by RNA-type (nucleobase pairing)-driven molecular imprinting. The prepolymerization complex stoichiometry involved one FU molecule and two molecules of the Ade-BTM functional monomer. Molecular structure of this complex was thermodynamically optimized via density functional theory at the B3LYP/3-21G* level. The stability constant of the FU-Ade-BTM complex of 1:2 stoichiometry was K = 2.17(±0.07) × 10(7) M(-2), as determined by titration with quenching of fluorescence of the bis(2,2'-bithienyl)methane moiety of Ade-BTM by the FU titrant, in benzonitrile, at 352 nm excitation. Next, (5-fluorouracil)-templated molecularly imprinted polymer (MIP-FU) films were deposited on indium-tin oxide (ITO) or Au film-coated glass slides, Pt disk electrodes, or 10-MHz quartz crystal resonators by potentiodynamic electropolymerization from solution of FU, Ade-BTM, and tris([2,2'-bithiophen]-5-yl)methane (TTM) cross-linking monomer at FU:Ade-BTM:TTM = 1:2:3 mol ratio. Then UV-visible and Fourier transform infrared (FT-IR) spectra of the MIP-FU films were recorded to confirm the FU template presence in the MIP-FU film and its subsequent release by extraction with methanol from this film. For determination of the stability constant of the complex of the MIP cavity and FU, piezoelectric microgravimetry (PM) under both batch- and flow-injection analysis conditions was used. For sensing application, three different transduction platforms [differential pulse voltammetry (DPV), capacitive impedimetry (CI), and PM] were integrated with the MIP-FU recognition unit. The limit of detection (LOD) was 56 nM, 75 nM, and 0.26 mM, for these chemosensors, respectively, indicating suitability of the former two for FU determination in blood plasma or serum (~500 nM). Moreover, the CI chemosensor was appreciably more sensitive to FU than to their common interferences.

Piezomicrogravimetric and impedimetric oligonucleotide biosensors using conducting polymers of biotinylated bis(2,2'-bithien-5-yl)methane as recognition units.

A new conducting polymer of biotinylated bis(2,2'-bithien-5-yl)methane was prepared and applied as the recognition unit of two different biosensors for selective oligonucleotide determination using either electrochemical impedance spectroscopy (EIS) or piezoelectric microgravimetry (PM) for label-free analytical signal transduction. For preparation of this unit, first, a biotinylated bis(2,2'-bithien-5-yl)methane functional monomer was designed and synthesized. Then, this monomer was potentiodynamically polymerized to form films on the surface of a glassy carbon electrode (GCE) and a Au electrode of a quartz crystal resonator (QCR) for the EIS and PM transduction, respectively. On top of these films, neutravidin was irreversibly immobilized by complexing the biotin moieties of the polymer. Finally, recognizing biotinylated oligonucleotide was attached by complexing the surface-immobilized neutravidin. This layer-by-layer assembling of the poly(thiophene-biotin)-neutravidin-(biotin-oligonucleotide) recognition film served to determine the target oligonucleotide via complementary nucleobase pairing. Under optimized determination conditions, the target oligonucleotide limit of detection (LOD) was 0.5 pM and 50 nM for the EIS and PM transduction, respectively. The sensor response to the target oligonucleotide was linear with respect to logarithm of the target oligonucleotide concentration in a wide range of 0.5 pM to 30 µM and with respect to its concentration in the range of 50 to 600 nM for the EIS and PM transduction, respectively. The biosensors were appreciably selective with respect to the nucleobase mismatched oligonucleotides.

Electroactive molecularly imprinted polymer nanoparticles for selective glyphosate determination.

Redox-active molecularly imprinted polymer nanoparticles selective for glyphosate, MIP-Gly NPs, were devised, synthesized, and subsequently integrated onto platinum screen-printed electrodes (Pt-SPEs) to fabricate a chemosensor for selective determination of glyphosate (Gly) without the need for redox probe in the test solution. That was because, ferrocenylmethyl methacrylate was added to the polymerization mixtures during the NPs synthesis so that the resulting MIP-Gly NPs contained covalently immobilized ferrocenyl moieties as the reporting redox ingredient, conferring these NPs with electroactive properties. MIP-Gly NPs of four different compositions were evaluated. The herein described approach represents a simple and effective way to endow MIP NPs with electrochemical reporting capabilities with neither the need to functionalize them post-synthesis nor to use electrochemical mediators present in the tested solution during the analyte determinations. MIP-Gly NPs synthesized using allylamine and squaramide-based monomers appeared most selective to Gly. The Pt-SPEs modified with MIP-Gly NPs were characterized with differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy (EIS). Changes in the DPV peak originating from the oxidation of the ferrocenyl moieties in these MIP-Gly NPs served as the analytical signal. The DPV limit of detection and the linear dynamic concentration range for Gly were 3.7 pM and 25 pM-500 pM, respectively. Moreover, the selectivity of the fabricated chemosensors was sufficiently high to determine Gly successfully in spiked river water samples.

Nicotine, cotinine, and myosmine determination using polymer films of tailor-designed zinc porphyrins as recognition units for piezoelectric microgravimetry chemosensors.

Two electropolymerizable zinc porphyrins with receptor sites tailor-designed for selective recognition of the nicotine, cotinine, or myosmine alkaloids were synthesized. These were 5-(2-phenoxyacetamide)-10,15,20-tris(triphenylamino)porphyrinato zinc(II) 1 and 5-(2,5-phenylene-bis(oxy)diacetamide)-10,15,20-tris(triphenylamino)porphyrinato zinc(II) 2 featuring one and two pendant amide side "pincers", respectively, and three triphenylamine substituents at the meso positions of the porphyrin macrocycles capable of electrochemical polymerization. Thin polymerfilms of these porphyrins served for recognition and the piezoelectric microgravimetry (PM) for analytical signal transduction of a new chemical sensor devised for determination of these alkaloids. The films were deposited by potentiodynamic electropolymerization on the 10 MHz quartz resonators of the electrochemical quartz crystal microbalance (EQCM) without affecting the electronic structure of the porphyrin macrocycles. Under favorable flow injection analysis (FIA) conditions, the alkaloid analytes were determined at the concentration level of 0.1 mM with high sensitivity and selectivity. Affinity toward the analytes of the polymer of 2 was higher than that of 1 due to the higher binding ability offered by two pendant pincers of the former. Because of the selective receptors and PM applied under FIA conditions, the developed procedure offered an alternative to the time-consuming and relatively expensive high-performance liquid chromatography (HPLC), capillary electrophoresis (CE), and gas chromatography mass spectrometry (GC-MS) methods of detection and quantification of these alkaloids.

Electrochemically synthesized polymers in molecular imprinting for chemical sensing.

This critical review describes a class of polymers prepared by electrochemical polymerization that employs the concept of molecular imprinting for chemical sensing. The principal focus is on both conducting and nonconducting polymers prepared by electropolymerization of electroactive functional monomers, such as pristine and derivatized pyrrole, aminophenylboronic acid, thiophene, porphyrin, aniline, phenylenediamine, phenol, and thiophenol. A critical evaluation of the literature on electrosynthesized molecularly imprinted polymers (MIPs) applied as recognition elements of chemical sensors is presented. The aim of this review is to highlight recent achievements in analytical applications of these MIPs, including present strategies of determination of different analytes as well as identification and solutions for problems encountered.

Polytyramine Film-Coated Single-Walled Carbon Nanotube Electrochemical Chemosensor with Molecularly Imprinted Polymer Nanoparticles for Duloxetine-Selective Determination in Human Plasma.

We devised, fabricated, and tested differential pulse voltammetry (DPV) and impedance spectroscopy (EIS) chemosensors for duloxetine (DUL) antidepressant determination in human plasma. Polyacrylic nanoparticles were synthesized by precipitation polymerization and were molecularly imprinted with DUL (DUL-nanoMIPs). Then, together with the single-walled carbon nanotube (SWCNT) scaffolds, they were uniformly embedded in polytyramine films, i.e., nanoMIPs-SWCNT@(polytyramine film) surface constructs, deposited on gold electrodes by potentiodynamic electropolymerization. These constructs constituted recognition units of the chemosensors. The molecular dynamics (MD) designing of DUL-nanoMIPs helped select the most appropriate functional and cross-linking monomers and determine the selectivity of the chemosensor. Three different DUL-nanoMIPs and non-imprinted polymer (nanoNIPs) were prepared with these monomers. DUL-nanoMIPs, synthesized from respective methacrylic acid and ethylene glycol dimethyl acrylate as the functional and cross-linking monomers, revealed the highest affinity to the DUL analyte. The linear dynamic concentration range, extending from 10 pM to 676 nM DUL, and the limit of detection (LOD), equaling 1.6 pM, in the plasma were determined by the DPV chemosensor, outperforming the EIS chemosensor. HPLC-UV measurements confirmed the results of DUL electrochemical chemosensing.

Molecularly imprinted polymer-based extended-gate field-effect transistor (EG-FET) chemosensor for selective determination of matrix metalloproteinase-1 (MMP-1) protein.

A conducting molecularly imprinted polymer (MIP) film was integrated with an extended-gate field-effect transistor (EG-FET) transducer to determine epitopes of matrix metalloproteinase-1 (MMP-1) protein biomarker of idiopathic pulmonary fibrosis (IPF) selectively. Most suitable epitopes for imprinting were selected with Basic Local Alignment Search Tool software. From a pool of MMP-1 epitopes, the two, i.e., MIAHDFPGIGHK and HGYPKDIYSS, the relatively short ones, most promising for MMP-1 determination, were selected, mainly considering their advantageous outermost location in the protein molecule and stability against aggregation. MIPs templated with selected epitopes of the MMP-1 protein were successfully prepared by potentiodynamic electropolymerization and simultaneously deposited as thin films on electrodes. The chemosensors, constructed of MIP films integrated with EG-FET, proved useful in determining these epitopes even in a medium as complex as a control serum. The limit of detection for the MIAHDFPGIGHK and HGYPKDIYSS epitope was ∼60 and 20 nM, respectively. Moreover, the chemosensors selectively recognized whole MMP-1 protein in the 50-500 nM concentration range in buffered control serum samples.

Cilostazol-imprinted polymer film-coated electrode as an electrochemical chemosensor for selective determination of cilostazol and its active primary metabolite.

An electrochemical chemosensor for cilostazol (CIL) determination was devised, engineered, and tested. For that, a unique conducting film of the functionalized thiophene-appended carbazole-based polymer, molecularly imprinted with cilostazol (MIP-CIL), was potentiodynamically deposited on a Pt disk electrode by oxidative electropolymerization. Thanks to electro-oxidation potentials lower than that of CIL, the carbazole monomers outperformed pyrrole, thiophene, and phenol monomers, in this electropolymerization. The pre-polymerization complexes quantum-mechanical and molecular dynamics analysis allowed selecting the most appropriate monomer from the three thiophene-appended carbazoles examined. The electrode was then used as a selective CIL chemosensor in the linear dynamic concentration range of 50 to 924 nM with a high apparent imprinting factor, IF = 10.6. The MIP-CIL responded similarly to CIL and CIL's pharmacologically active primary metabolite, 3,4-dehydrocilostazol (dhCIL), thus proving suitable for their determination together. Simulated models of the MIP cavities binding of the CIL, dhCIL, and interferences' molecules allowed predicting chemosensor selectivity. The MIP film sorption of CIL and dhCIL was examined using DPV by peak current data fitting with the Langmuir (L), Freundlich (F), and Langmuir-Freundlich (LF) isotherms. The LF isotherm best described this sorption with the sorption equilibrium constant (KLF) for CIL and dhCIL of 12.75 × 10-6 and 0.23 × 10-6 M, respectively. Moreover, the chemosensor cross-reactivity to common interferences study resulted in the selectivity to cholesterol and dehydroaripiprazole of 1.52 and 8.0, respectively. The chemosensor proved helpful in determining CIL and dhCIL in spiked human plasma with appreciable recovery (99.3-134.1%) and limit of detection (15 nM).

Peptide Selection of MMP-1 for Electrochemical Sensing with Epitope-Imprinted Poly(TPARA-co-EDOT)s.

Instead of molecularly imprinting a whole protein molecule, imprinting protein epitopes is gaining popularity due to cost and solubility issues. Belonging to the matrix metalloproteinase protein family, MMP-1 is an interstitial collagenase that degrades collagen and may be involved in cell migration, cell proliferation, the pro-inflammatory effect, and cancer progression. Hence, it can serve as a disease protein biomarker and thus be useful in early diagnosis. Herein, epitopes of MMP-1 were identified by screening its crystal structure. To identify possible epitopes for imprinting, MMP-1 was cleaved in silico with trypsin, pepsin at pH = 1.3, and pepsin at pH > 2.0 using Peptide Cutter, generating peptide fragments containing 8 to 12 amino acids. Five criteria were applied to select the peptides most suitable as potential epitopes for MMP-1. The triphenylamine rhodanine-3-acetic acid (TPARA) functional monomer was synthesized to form a stable pre-polymerization complex with a selected template epitope. The complexed functional monomer was then copolymerized with 3,4-ethoxylenedioxythiophene (EDOT) using potentiodynamic electropolymerization onto indium−tin−oxide (ITO) electrodes. The composition of the molecularly imprinted poly(TPARA-co-EDOT) (MIP) was optimized by maximizing the film's electrical conductivity. Cyclic voltammetry was used to determine MMP-1 concentration in the presence of the Fe(CN)63−/Fe(CN)64− redox probe actuating the "gate effect." A calibration curve was constructed and used to determine the usable concentration range and the limit of detection as ca. 0.001 to 10.0 pg/mL and 0.2 fg/mL MMP-1, respectively. Finally, the MMP-1 concentration in the A549 human lung (carcinoma) culture medium was measured, and this determination accuracy was confirmed using an ELISA assay.

Molecularly imprinted polymer nanoparticles-based electrochemical chemosensors for selective determination of cilostazol and its pharmacologically active primary metabolite in human plasma.

Molecularly imprinted polymer (MIP) nanoparticles-based differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy (EIS) chemosensors for antiplatelet drug substance, cilostazol (CIL), and its pharmacologically active primary metabolite, 3,4-dehydrocilostazol (dhCIL), selective determination in human plasma were devised, prepared, and tested. Molecular mechanics (MM), molecular dynamics (MD), and density functional theory (DFT) simulations provided the optimum structure and predicted the stability of the pre-polymerization complex of the CIL template with the chosen functional acrylic monomers. Moreover, they accounted for the MIP selectivity manifested by the molecularly imprinted cavity with the CIL molecule complex stability higher than that for each interference. On this basis, a fast and reliable method for determining both compounds was developed to meet an essential requirement concerning the personalized drug dosage adjustment. The limit of detection (LOD) at the signal-to-noise ratio of S/N = 3 in DPV and EIS determinations using the ferrocene redox probe in a "gate effect" mode was 93.5 (±2.2) and 86.5 (±4.6) nM CIL, respectively, and the linear dynamic concentration range extended from 134 nM to 2.58 µM in both techniques. The chemosensor was highly selective to common biological interferences, including cholesterol and glucose, and less selective to structurally similar dehydroaripiprazole. Advantageously, it responded to dhCIL, thus allowing for the determination of CIL and dhCIL together. The EIS chemosensor appeared slightly superior to the DPV chemosensor concerning its selectivity to interferences. The CIL DPV sorption data were fitted with Langmuir, Freundlich, and Langmuir-Freundlich isotherms. The determined sorption parameters indicated that the imprinted cavities were relatively homogeneous and efficiently interacted with the CIL molecule.

Molecularly imprinted polymer as a synthetic receptor mimic for capacitive impedimetric selective recognition of Escherichia coli K-12.

We fabricated an electrochemical molecularly imprinted polymer (MIP) chemosensor for rapid identification and quantification of E. coli strain using 2-aminophenyl boronic acid as the functional monomer. This strain is a modified Gram-negative strain of Escherichia coli bacterium, an ordinary human gut component. The E. coli strongly interacts with a boronic acid because of porous and flexible polymers of the cell wall. The SEM imaging showed that the bacteria template was partially entrapped within the polymeric matrix in a single step. Moreover, this imaging confirmed E. coli K-12 cell template extraction effectiveness. The prepared MIP determined the E. coli K-12 strain up to 2.9 × 104 cells mL-1. The interference study performed in the presence of E. coli variants expressing different surface appendages (type 1 fimbriae or Antigen 43 protein) or Shewanella oneidensis MR1, another Gram-negative bacteria, demonstrated that the bacterial surface composition notably impacts sensing properties of the bacteria imprinted polymer.

Electrochemical sensor for selective tyramine determination, amplified by a molecularly imprinted polymer film.

A molecularly imprinted polymer (MIP) film based electrochemical sensor for selective determination of tyramine was devised, fabricated, and tested. Tyramine is generated in smoked and fermented food products. Therefore, it may serve as a marker of the rottenness of these products. Importantly, intake of large amounts of tyramine by patients treated with monoamine oxidase (MAO) inhibitors may lead to a "cheese effect", namely, a dangerous hypertensive crisis. The limit of detection at S/N = 3 of the chemosensor, in both differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy (EIS) determinations, with the use of the Fe(CN)64-/Fe(CN)63- redox probe, was 159 and 168 µM tyramine, respectively. The linear dynamic concentration range was 290 µM to 2.64 mM tyramine. The chemosensor was highly selective with respect to the glucose, urea, and creatinine interferences. Its DPV determined apparent imprinting factor was 5.6. Moreover, the mechanism of the "gate effect" in the operation of the polymer film-coated electrodes was unraveled.

Selective histamine piezoelectric chemosensor using a recognition film of the molecularly imprinted polymer of bis(bithiophene) derivatives.

A histamine piezoelectric (acoustic) sensor using a molecularly imprinted polymer (MIP) film has been devised and tested. The sensor comprises an electrodeposited MIP film as the recognition element and a 10 MHz AT-cut shear-thickness-mode bulk-acoustic-wave quartz crystal resonator with Pt film electrodes as the signal transducer. Preparation of the sensing film involved two consecutive electrochemical polymerizations, performed under cyclic voltammetric conditions, with the use of a supporting electrolyte of 0.1 M tetra-n-butylammonium perchlorate in acetonitrile. First, a poly(bithiophene) barrier film was deposited by electropolymerization on the Pt/quartz resonator to prevent histamine electro-oxidation and avoid possible contamination of the Pt electrode surface. Next, the histamine-templated MIP film was deposited by electropolymerization on top of this barrier film. For that purpose, two functional monomers of bis(bithiophene) derivatives, i.e., one bearing the 18-crown-6 and the other dioxoborinane substituent, were copolymerized in the presence of the histamine template. The consecutive growth of both these overlaid films was monitored with an electrochemical quartz crystal microbalance (EQCM). Subsequently, the histamine was extracted from MIP with 0.01 M NaOH for 12 h. The UV-vis and X-ray photoelectron spectroscopic measurements confirmed the completeness of the removal of the histamine template from the MIP film. The analytical performance of the chemosensor was assessed under flow injection analysis (FIA) conditions using the carrier 0.5 M HEPES buffer (pH = 7.5) solution and the piezoelectric microgravimetry detection at QCM. The negative peaks of resonant frequency linearly decreased with the increase of the histamine concentration in the range 10-100 mM for 150 microL/min flow rate, and 100 microL volume of the injected sample. The sensitivity of the chemosensor (0.33 Hz/mM) was more than twice as that of the chemosensor without the poly(bithiophene) barrier film (0.15 Hz/mM). The chemosensor performance was superior for selective histamine recognition if the poly(bithiophene) barrier film thickness exceeded 200 nm. The chemosensor discriminated histamine from functionally or structurally similar compounds, such as dopamine, tryptamine, and imidazole. Stability constants of the affinity complexes of MIP and analyte or the interfering agent were determined from kinetic studies. For the MIP-histamine complex, the stability constant thus evaluated was equal to 57.0 M(-1) being much higher than those for the MIP-tryptamine and MIP-dopamine complexes determined to be 10.7, and 6.4 M(-1), respectively. The concentration limit of detection was as low as 5 nM histamine if the carrier solution flow rate was as low as 35 microL/min and the injection sample volume as large as 1 mL.

Melamine acoustic chemosensor based on molecularly imprinted polymer film.

A melamine piezomicrogravimetric (acoustic) chemosensor using a molecularly imprinted polymer (MIP) film has been devised and tested. The MIP films were prepared by electropolymerization of the melamine complexed by the functional monomer of the bis(bithiophene) derivative bearing an 18-crown-6 substituent 4. The structure of the MIP-melamine complex was visualized by the DFT B3LYP/3-21G(*) energy optimization calculations. The sensitivity and selectivity of the MIP film was improved by cross-linking the polymer with the bithianaphthene monomer 5 and the presence of the porogenic ionic liquid in the prepolymerization solution. After electropolymerization, the melamine template was extracted from the MIP film with an aqueous strong base solution. The measurements of UV-vis spectroscopy, X-ray photoelectron spectroscopy (XPS), DPV, and EIS as well as scanning electrochemical microscopy (SECM) imaging confirmed extraction of the melamine template from the MIP film and then rebinding of the melamine analyte while the film relative roughness and porosity was determined by atomic force microscopy (AFM) and scanning electron microscopy (SEM) imaging, respectively. The analytical as well as kinetic and thermodynamic parameters of the chemosensing were assessed under flow-injection analysis (FIA) conditions with piezoelectric microgravimetry (PM) detection. The linear concentration range for melamine detection was 5 nM to at least 1 mM with a limit of detection of approximately 5 nM. The chemosensor successfully discriminated the cyanuric acid, cyromazine, and ammeline interfering agents.

Oligonucleotide Analogs and Mimics for Sensing Macromolecular Biocompounds.

Living organisms create life-sustaining macromolecular biocompounds including biopolymers. Artificial polymers can selectively recognize biocompounds and are more resistant to harsh physical, chemical, and physiological conditions than biopolymers are. Due to recognition at a molecular level, molecularly imprinted polymers (MIPs) provide powerful tools to correlate structure with biological functionality and are often used to build next-generation chemosensors. We envision an increasing emergence of nucleic acid analogs (NAAs) or biorelevant monomers built into nature-mimicking polymers. For example, if nucleobases bearing monomers arranged by a complementary template are polymerized to form NAAs, the resulting MIPs will open up novel perspectives for synthesizing NAAs. Despite their usefulness, it is still challenging to use MIPs to devise adaptive biomaterials and to implement them in point-of-care testing.